Depressive disorders account for substantial morbidity and mortality among children and adolescents and are most commonly treated with antidepressants. In recent years, increasing concerns have arisen that antidepressants in and of themselves might increase the risk of suicidality specifically among children and adolescents. However, the available evidence regarding suicidality and antidepressants in children is limited due to the small sample size of the clinical trials (even when combined in meta-analysis) resulting in insufficient power to assess the risk of suicide deaths and the risk of suicide-related behaviors for individual antidepressants. In addition, the short duration of clinical trials has precluded assessment of the risk of serious suicide attempts and suicidality over the course of treatment. Understanding the relationship between antidepressant treatment and injuries from suicidal behavior in children and adolescents is vital for clinical practice. The research described in this proposal will address three specific aims: 1) test the hypothesis that the risk of medically treated suicide attempts is lower for fluoxetine than for other antidepressants;2) test the hypothesis that the risk of medically treated suicide attempts is increased in the time 4 and 12 weeks following initiation of antidepressant therapy;and, 3) test the hypothesis that periods on antidepressants represent greater risk for medically treated suicide attempts and suicide deaths than periods off antidepressants. To address these aims, a retrospective study cohort will be assembled from Tennessee Medicaid files and will include an estimated 85,000 6-18 year old children who are users of antidepressant medications with evidence suggesting treatment of major depression. Cohort follow up will be from 1995-2006 and will include an estimated 73,000 person-years of follow-up. Every person-day of follow-up will be classified by exposure to study medications and potential confounding factors. A case definition drawn from Medicaid claims, death certificates, and confirmed through medical record review will define medically treated suicide attempts and suicide deaths among children in the cohort. Poisson regression will be used to estimate the effects of the individual study drugs and the duration of study drug exposure on study endpoints. A case-crossover design will compare risk for periods on vs. off antidepressants. This research will address questions of enormous public health importance. Patients, families, and physicians urgently need to know whether or not individual drugs affect the risk of suicidality differently. Whether or not risk is increased early in the course of treatment will have implications for monitoring of children on these medications. Finally, understanding the risk of suicidality for periods off and on treatment will inform practitioners, patients, and families faced with treating an important condition.